Fluid delivery device with hydrophobic surface

ABSTRACT

Embodiments of the present invention are directed to a liquid delivery apparatus. A non-limiting example of the apparatus includes a substrate including a cavity formed in a surface of the substrate. The apparatus can also include a membrane disposed on the surface of the substrate covering an opening of the cavity. The apparatus can also include a hydrophobic layer disposed on the membrane. The apparatus can also include a seal disposed between the membrane and the substrate, wherein the seal surrounds the opening of the cavity. The apparatus can also include an electrode layer coupled to the membrane.

DOMESTIC PRIORITY

This application is a divisional of U.S. application Ser. No. 15/656,126entitled “FLUID DELIVERY DEVICE WITH HYDROPHOBIC SURFACE,” filed Jul.21, 2017, the contents of which are incorporated herein by reference inits entirety.

BACKGROUND

The present invention generally relates to miniaturized delivery devicesand related methods, and more specifically to liquid delivery deviceswith hydrophobic surfaces and related methodologies.

Micro-scale delivery devices can be useful in a variety of applications.Such delivery devices can include an array of micro-scale reservoirsfilled with small amounts of material such as liquids or powders. Thereservoirs are sealed with material and can provide controlled deliveryof the material, for example, by rupture or melting of a metal membrane.Such micro-scale delivery devices can provide independent and controlledrelease of materials in individual reservoirs and can, for example, beuseful in drug delivery applications.

In some applications, achieving the desired size of the micro-scaledelivery device can place severe constraints on energy storage and powerdelivery. For example, smaller sizes of implantable and wearable drugdelivery devices can be preferred for patient comfort and privacy.Reservoir release of the material, however, requires energy and,moreover, can be subject to major sources of energy loss through thermalconduction within the device structure. Reservoirs containing liquids,for instance, can experience undesirably high thermal conduction. Thus,there remains a need to minimize energy required for reservoir release.

SUMMARY

Embodiments of the present invention are directed to a liquid deliveryapparatus. A non-limiting example of the apparatus includes a firstsubstrate including a reservoir formed in the first substrate. Theapparatus can also include a membrane disposed on the surface of thefirst substrate covering an opening of the reservoir. The membrane caninclude, in some embodiments of the invention, a metal layer, anelectrically-insulating dielectric layer, or a combination of metallicand insulating structures. The apparatus can also include a secondsubstrate bonded to the first substrate, wherein the second substrateincludes a reservoir seal. The apparatus can also include a hydrophobiclayer disposed on an inside surface of the membrane. The apparatus canalso include an electrode in electrical contact with the membrane. Suchembodiments can provide activation by melting or fracturing the membraneand provide automated delivery of a liquid with minimized energy lossesdue to thermal conduction of the liquids.

Embodiments of the present invention are directed to a liquid deliveryapparatus. A non-limiting example of the apparatus includes a substrateincluding a cavity formed in a surface of the substrate. The apparatuscan also include a membrane connected to a hinged structure. Theapparatus can also include a hydrophobic layer disposed on the membrane.The apparatus can also include a seal disposed between the membrane andthe substrate, wherein the seal surrounds the opening of the cavity.Such embodiments can provide device activation by melting or breakingthe seal, providing automated delivery of a liquid with reduced releaseof membrane or seal debris.

Embodiments of the present invention are directed to an electronicdelivery device. A non-limiting example of the device includes adispensing array including a plurality of reservoirs. The dispensingarray can include a cavity, a membrane covering an opening of thecavity, and a hydrophobic layer disposed on the membrane. The device canalso include a microprocessor in communication with the dispensingarray. The device can also include a wireless receiver in communicationwith the microprocessor. Such embodiments can provide energy efficientremote release of fluids from a dispensing array in a miniaturizeddelivery device.

Embodiments of the present invention are directed to a method ofdelivering liquids. A non-limiting example of delivering the liquidsincludes forming a hydrophobic liner on a release membrane covering adelivery structure reservoir. The method also includes depositing aliquid in the reservoir. The method also includes sealing the reservoirwith a hydrophilic layer. The method also includes providing an electriccurrent to the release membrane to dispense the liquid. Such embodimentscan preserve integrity of liquids for automated release in electronicdelivery devices.

Embodiments of the present invention are directed to a computer programproduct for delivery of liquids. The computer program product caninclude a computer readable storage medium having program instructionsembodied therewith, wherein the instructions are executable by aprocessor to perform a method. A non-limiting example of the methodincludes receiving a signal from a sensor concerning a localenvironmental condition. The method can also include sending, based atleast in part upon the signal, an electric current to a release membranelined with a hydrophobic liner, wherein the release membrane covers adelivery structure reservoir. The method can also include rupturing themembrane with the electric current.

Additional technical features and benefits are realized through thetechniques of the present invention. Embodiments and aspects of theinvention are described in detail herein and are considered a part ofthe claimed subject matter. For a better understanding, refer to thedetailed description and to the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The specifics of the exclusive rights described herein are particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The foregoing and other features and advantages ofthe embodiments of the invention are apparent from the followingdetailed description taken in conjunction with the accompanying drawingsin which:

FIG. 1 depicts a block diagram illustrating one example of a processingsystem according to one or more embodiments of the present invention.

FIG. 2A depicts an exemplary system according to one or more embodimentsof the present invention.

FIG. 2B depicts another view of the exemplary system of FIG. 2Aaccording to one or more embodiments of the present invention.

FIG. 3A depicts an exemplary system according to one or more embodimentsof the present invention.

FIG. 3B depicts another view of the exemplary system of FIG. 3Aaccording to one or more embodiments of the present invention.

FIG. 4A depicts an exemplary system according to one or more embodimentsof the present invention.

FIG. 4B depicts another view of the exemplary system of FIG. 3Aaccording to one or more embodiments of the present invention.

FIG. 5 depicts a block diagram of control circuitry according to one ormore embodiments of the present invention.

FIG. 6 depicts a flow diagram of an exemplary method according to one ormore embodiments of the present invention.

FIG. 7 depicts a flow diagram of an exemplary method according to one ormore embodiments of the present invention.

The diagrams depicted herein are illustrative. There can be manyvariations to the diagram or the operations described therein withoutdeparting from the spirit of the invention. For instance, the actionscan be performed in a differing order or actions can be added, deletedor modified. Also, the term “coupled” and variations thereof describeshaving a communications path between two elements and does not imply adirect connection between the elements with no interveningelements/connections between them. All of these variations areconsidered a part of the specification.

In the accompanying figures and following detailed description of thedescribed embodiments, the various elements illustrated in the figuresare provided with two or three digit reference numbers. With minorexceptions, the leftmost digit(s) of each reference number correspond tothe figure in which its element is first illustrated.

DETAILED DESCRIPTION

For the sake of brevity, conventional techniques related tosemiconductor device and integrated circuit (IC) fabrication may or maynot be described in detail herein. Moreover, the various tasks andprocess steps described herein can be incorporated into a morecomprehensive procedure or process having additional steps orfunctionality not described in detail herein. In particular, varioussteps in the manufacture of semiconductor devices andsemiconductor-based ICs are well known and so, in the interest ofbrevity, many conventional steps will only be mentioned briefly hereinor will be omitted entirely without providing the well-known processdetails.

Turning now to an overview of technologies that are more specificallyrelevant to aspects of the invention, digital delivery devices can bedesirable in applications that can benefit from precise schedulingand/or release of precise amounts of material in an automatic fashion.For instance, in drug delivery applications, digital delivery devicescan include a plurality of reservoirs that can be independently and/orremotely released according to a precise dosage and schedule. In somecases, including pharmaceutical and non-pharmaceutical applications,digital delivery devices can be used to provide release of an agent forprecise or automated initiation or termination of a chemical reaction.For example, in microbattery applications, digital release of anelectrolyte from a reservoir can activate the microbattery remotely. Inanother application, an array of biosensors, contained in a backplane,are configured to respond to specific biomarkers following chemicalactivation. Prior to use, the biosensor surfaces can be cleaned. Theindividual biosensors can be sealed and protected by a membrane, andeach biosensor can be in close proximity to a reservoir containing aliquid chemical that activates the biosensor surface for analytebiomarker detection. Upon application of an activation signal, themembrane containing the activation chemical reservoir and the membranesealing the biosensor are both opened. In some cases, moreover, digitaldelivery devices can be interfaced to sensor systems to provide anautomatic closed-loop drug delivery system.

The ability to remotely release materials from digital delivery devicesmakes them potentially useful in implantable or wearable devices. Forexample, treatment of some medical conditions can call foradministration of agents that are not suitable or optimal for oraladministration or for delivery of agents according to a precise dosageand schedule. For such applications, drug delivery implants havepotential to provide administration of agents according to a preciseschedule with minimal involvement of a patient or health care provider.In addition to implanted systems, digital delivery devices could providesimilar delivery benefits in wearable (e.g., transdermal, transmucosal,etc.) systems, such as in adhesive patch systems.

Inclusion of digital delivery devices in applications in which devicesize is important, such as in implantable or wearable devices, can posechallenges in system design. Aside from any patient and health careprovider preferences for small devices for patient comfort, there can bephysical limitations on the size of devices that can be implanted intoor worn by the patient. As such, smaller device volumes cansignificantly constrain energy storage and power delivery. Minimizingthe energy required for reservoir release can improve device design andperformance.

Thermal conduction within the device structure can be a major source ofenergy loss in digital delivery devices. For instance, reservoirsincluding liquids can experience high thermal conduction.

Conventional digital delivery devices can include a destructible metalmembrane covering a reservoir. To obtain release of an agent from thereservoir, the membrane can be activated by providing an electriccurrent sufficient to rupture or melt the membrane and, thereby, exposethe reservoir opening to the surrounding environment. However, liquidsare good thermal conductors. Prior to rupture or melt of the membrane,liquid in the reservoir or cavity that is in contact with the membranewill draw additional energy from the system. Energy drawn from thesystem can, moreover, vaporize the liquid that is in contact with themembrane. Such vaporization can not only require additional heat but canalso potentially degrade or damage temperature sensitive agents in thereservoir.

Some conventional digital delivery devices can include releasablemembranes, such membranes attached to the device body via a hinge. Uponactivation through application of energy to the system, the membrane canpartially release from the structure, exposing liquid in a reservoir orcavity to the surrounding environment. For reasons similar to thosenoted above, liquids in contact with the sealing rings of such devicescan increase the energy needed to open the membrane.

Conventional methods of reducing liquid reservoir energy inefficienciescan include lyophilizing intended reservoir materials to reduce and/oreliminate reservoir liquids. Lyophilization (freeze drying) is a processin which water is removed from a sample by freezing a solution ofinterest and sublimating the water from the frozen solution under lowpressure, leaving behind a dried or powdered sample. However,lyophilization, in addition to requiring additional expense andprocessing steps, can be unsuitable for certain compounds and, further,can require additional reconstitution steps before administering thedesired agent to its target. Moreover, lyophilization can often requirelarge batch processing to be cost-effective. A need remains to reducethermal conduction in digital delivery systems, in particular in systemsthat include liquid reservoir materials.

Turning now to an overview of the aspects of the invention, one or moreembodiments of the invention address the above-described shortcomings ofthe prior art by providing a hydrophobic layer on the release membraneof a digital delivery device. In some embodiments of the invention, areservoir is sealed at an end opposite the membrane and hydrophobiclayer with a second substrate. The second substrate can include, in someembodiments of the invention, a hydrophilic surface. Such embodiments ofthe invention can draw the liquid to the hydrophilic surface and awayfrom the membrane

The above-described aspects of the invention address the shortcomings ofthe prior art by reducing thermal conduction in the device structure byrepelling liquid substances from the reservoir or cavity away from themembrane. In some embodiments of the invention, liquid in the reservoiris drawn to a hydrophilic surface opposite the hydrophobic layer and themembrane. In some embodiments of the invention, the hydrophobic layerprovides formation of an air pocket between a reservoir fluid surfaceand the membrane, in which the air pocket provides thermal insulationand improved thermal properties.

Referring to FIG. 1 , there is shown an embodiment of a processingsystem 100 for implementing the teachings herein. In this embodiment ofthe invention, the system 100 has one or more central processing units(processors) 101 a, 101 b, 101 c, etc. (collectively or genericallyreferred to as processor(s) 101). In one embodiment of the invention,each processor 101 can include a reduced instruction set computer (RISC)microprocessor. Processors 101 are coupled to system memory 114 andvarious other components via a system bus 113. Read only memory (ROM)102 is coupled to the system bus 113 and can include a basicinput/output system (BIOS), which controls certain basic functions ofsystem 100.

FIG. 1 further depicts an input/output (I/O) adapter 107 and a networkadapter 106 coupled to the system bus 113. I/O adapter 107 can be asmall computer system interface (SCSI) adapter that communicates with ahard disk 103 and/or tape storage drive 105 or any other similarcomponent. I/O adapter 107, hard disk 103, and tape storage device 105are collectively referred to herein as mass storage 104. Operatingsystem 120 for execution on the processing system 100 can be stored inmass storage 104. A network adapter 106 interconnects bus 113 with anoutside network 116 enabling data processing system 100 to communicatewith other such systems. A screen (e.g., a display monitor) 115 isconnected to system bus 113 by display adaptor 112, which can include agraphics adapter to improve the performance of graphics intensiveapplications and a video controller. In one embodiment of the invention,adapters 107, 106, and 112 can be connected to one or more I/O bussesthat are connected to system bus 113 via an intermediate bus bridge (notshown). Suitable I/O buses for connecting peripheral devices such ashard disk controllers, network adapters, and graphics adapters typicallyinclude common protocols, such as the Peripheral Component Interconnect(PCI). Additional input/output devices are shown as connected to systembus 113 via user interface adapter 108 and display adapter 112. Akeyboard 109, mouse 110, and speaker 111 all interconnected to bus 113via user interface adapter 108, which can include, for example, a SuperI/O chip integrating multiple device adapters into a single integratedcircuit.

In exemplary embodiments of the invention, the processing system 100includes a graphics processing unit 130. Graphics processing unit 130 isa specialized electronic circuit designed to manipulate and alter memoryto accelerate the creation of images in a frame buffer intended foroutput to a display. In general, graphics processing unit 130 is veryefficient at manipulating computer graphics and image processing, andhas a highly parallel structure that makes it more effective thangeneral-purpose CPUs for algorithms where processing of large blocks ofdata is done in parallel.

Thus, as configured in FIG. 1 , the system 100 includes processingcapability in the form of processors 101, storage capability includingsystem memory 114 and mass storage 104, input means such as keyboard 109and mouse 110, and output capability including speaker 111 and display115. In one embodiment of the invention, a portion of system memory 114and mass storage 104 collectively store an operating system such as theAIX® operating system from IBM Corporation to coordinate the functionsof the various components shown in FIG. 1 .

Turning now to a more detailed description of aspects of the presentinvention, FIG. 2A depicts a hydrophobic delivery system 200 accordingto embodiments of the invention. The system 200 includes a firstsubstrate 210 including a reservoir 222 formed in the surface of thesubstrate 210. The system 200 can include a first sacrificial layer 212on top of the first substrate 210. The sacrificial layer 212 caninclude, for example, silicon nitride (SiN) or silicon dioxide (SiO₂).The system 200 can include an electrode layer including multilayer metalstack including a plurality of metal layers 214, 216, 218. The system200 can also include a membrane 220 in contact with one or more of themetal layers 214, 216, 218 and covering an opening of the reservoir 220.The membrane 220 can include a metal film, for example a metal film witha thickness of about 1 micron. The membrane 220 can include a metal thatcan be ruptured or melted upon activation and can include, for instance,gold, aluminum, indium, or a reactive material consisting of a stack ofmetal layers such a nickel and aluminum, or aluminum and palladium. Themembrane 220 can also include electrically-insulating dielectricmaterials such as silicon dioxide (SiO₂), silicon nitride (SiN_(x)), orpolymer materials. In some embodiments of the invention, the membrane220 includes a hydrophobic layer 224 on a surface facing the cavity 222.The system 200 can include a second sacrificial layer 226 on the bottomof the substrate 210. The second sacrificial layer 226 can include thesame material or a different material than the first sacrificial layer212, such as SiN_(x) or SiO₂. The system 200 can also include a sealinglayer 208 and reservoir seal 206. The sealing layer 208 and reservoirseal 206 can include a low melting point material, such as a metalcoated polymer layer including indium (In). The reservoir seal 206 canbe coupled to a second substrate 209 including a biocompatible layer 202coated with a metal compatible layer 204. In some embodiments of theinvention, the reservoir seal provides a permanent and/or irreversibleseal to the reservoir.

The sealing layer 208 and seal 206 can surround an opening of the cavity222 and can be configured to enclose the cavity 222 and retain asubstance within the cavity. While only one cavity 222 is shown forillustrative purposes, it is to be understood that the substrate 210 canbe formed with an array of cavities, including for instance hundreds ofcavities that serve as reservoirs for holding the same type or acombination of different types of deliverable substances.

The number of metal layers can vary dependent upon the desiredapplication of the system. For example, a system including a highernumber of reservoir types or with a relatively complex release schedulecan include a higher number of metal layers than a system includingfewer reservoir types or a simpler release schedule. The metal layers214, 216, 218, can include metallic material such as copper, gold,platinum, or titanium and can be in the form of metal layers or in theform of patterned layers including metallic electrode elements,including copper, gold, platinum, or titanium, formed in one or moresilicon dioxide layers. In some embodiments of the invention, electrodesare in electrical contact with the membrane, for instance providingelectric current to heat the membrane or a portion of the membrane. Themultilayer metal stack can be configured to locally heat a portion ofthe membrane 220.

The cavity 222 can have a diameter suitable to house a liquid in aquantity sufficient for the desired application, such as about 1 toabout 100 nanoliters (nL), or about 10 to about 50 nL of fluid. Forexample, the cavity 222 can have a diameter ranging from about 100microns to about 1 millimeter (mm) and can have a depth of about 100 toabout 500 microns.

The biocompatible layer 202 includes a biocompatible substrate, such asa substrate including polydimethylsiloxane (PDMS), silicon, glass,polyimide, such as KAPTON®, or a biocompatible cement. The metalcompatible layer 204 can include a material that can be coupled to theseal 206. In some embodiments of the invention, the metal compatiblelayer 204 includes gold.

The hydrophobic layer 224 can be deposited, grown or formed on thestructure, for instance by plasma deposition, surface treatment, coatingor nano-coating, electrodeposition. The hydrophobic layer 224 caninclude materials with a hydrophobicity sufficient to repel a desiredaqueous material in the reservoir. The hydrophobic layer can include forexample fluorocarbons, such as teflon, teflon-like materials, or otherplasma deposited hydrophobic fluorinated thin films; micro-structuredpolymers, such as PDMS or SU-8; nano-coatings such as coatings includingsilica particles, polytetrafluoroethylene (PTFE), or alumina particles;electrodepo sited metal films, such as porous electrodeposited metalfilms, for instance porous gold film; oxides and oxide composites, suchas manganese oxide polystyrene (MnO₂/PS) nano-composite or zinc oxidepolystyrene (ZnO/PS) nano-composite; precipitated calcium carbonate,carbon nanotubes; or patterned films, such as pillar and/or groovestructured films. In some embodiments of the invention, the hydrophobiclayer 224 lines only the membrane 220. In some embodiments of theinvention, the hydrophobic layer 224 lines the membrane and at leastpart of the cavity, such as the cavity walls adjacent to the membrane.The hydrophobic layer can have a thickness of about 5 Angstrom (Å) toabout 1 micron. In some embodiments of the invention, at least a portionof the membrane includes an electrically-insulating film.

FIG. 2B depicts the exemplary hydrophobic delivery system 200 of FIG. 2Aafter activation according to some embodiments of the invention. Afteractivation, membrane 220 and hydrophobic layer 224 are removed from thedevice, for instance by rupture or melt of the membrane upon stimulationwith an electric current, and the cavity 222 is accessible by the localenvironment.

Hydrophobic delivery systems according to embodiments of the inventioncan be fabricated using standard materials and semiconductor fabricationprocesses, including Micro-Electro-Mechanical (MEMS) technology, BackEnd Of the Line (BEOL) technology, photolithography, wafer bonding,wafer thinning, and wafer transfer processes, for example. In someembodiments of the invention, materials used for constructing deliverydevices include materials that are biocompatible or that can otherwisebe made biocompatible by coating with suitable biocompatible materials.

For example, the substrate 210 can be formed using any standardsemiconductor material such as silicon, or glass, ceramic, etc., whichcan be micro-machined or etched using standard etching processes (e.g.anisotropic wet chemical etching or deep reactive ion etching (DRIE))and wafer thinning processes, for example. The substrate 210 can beformed using a biocompatible material, such as silicon, which is notpermeable to the liquid contents contained in the etched cavities. Thedimensions and shape of the cavity 222 and the number of cavities formedin the substrate 210 will vary depending on the application. In oneembodiment of the invention, the cavities 222 are circular-shapedcavities that are formed in a silicon substrate using a deep RIEprocess. In other embodiments of the invention, the cavities can be inthe shape of truncated, four-sided pyramids formed by anisotropic wetetch of (100)-oriented silicon.

In some embodiments of the invention, a cavity 222 within a substratecan be filled with liquid prior to sealing the cavity 222. For example,a cavity 222 can be filled with a liquid prior to coupling the reservoirseal 206 to a second substrate 209. In such embodiments of theinvention, the sealing process implemented is one that does notadversely affect or otherwise disturb or degrade the deliverablesubstance filled within the cavity 222.

In some embodiments of the invention, hydrophobic delivery systems caninclude sensors. Sensors can include any sensing apparatus that usefulin a miniaturized or automated delivery system. Sensors can include, forexample, pH sensors, ionic sensors, heart rate sensors, blood pressuresensors, flow sensors, humidity sensors, action potential sensors, localfield potential sensors, chemical sensors, such as nucleic acid sensors,protein sensors, exosome sensors, glucose sensors, or neurotransmitterspecific sensors, optical sensors, or acoustic sensors.

FIG. 3A depicts the exemplary hydrophobic delivery system 200 of FIG. 2Ain an exemplary step of the process of filling the device with a fluid.The system 200 includes a substrate 210 including a cavity 222 formed inthe surface of the substrate 210. The system 200 can include a firstsacrificial layer 212 on top of the substrate 210. The sacrificial layer212 can include, for example, silicon nitride (SiN) or silicon dioxide(SiO₂). The system 200 can include a multilayer metal stack including aplurality of metal layers 214, 216, 218. The system 200 can also includea membrane 220 in contact with one or more of the metal layers 214, 216,218 and covering the cavity 220. The membrane 220 can include a thinmetal film, for example a metal film with a thickness of about 1 micron.The membrane 220 includes a metal that can be ruptured, melted, orpartially melted upon activation. Activation of the system to releasethe contents of a reservoir can include providing a high density currentflow through the membrane 220, for instance by way of one or moreelectrodes in contact with the membrane. The membrane 220 can include,for instance, aluminum, gold, or a reactive material such as layeredstructure of aluminum and palladium. A hydrophobic layer 224 lines aface of the membrane in the cavity 220. A drop of solution 230 can bedeposited in the cavity. As is shown in FIG. 3A, the hydrophobic layer224 can repel the solution 230 so as to minimize its contact with themembrane 220 and hydrophobic layer 224, for example by forming a bead.

FIG. 3B depicts the exemplary hydrophobic delivery system 200 of FIG. 3Aafter sealing the reservoir. The reservoir cavity 222 can be sealed witha second substrate 209. In some embodiments of the invention, the secondsubstrate 209 can include a hydrophilic surface 232. For example, ahydrophilic surface 232 can attract the liquid in the reservoir 230,further drawing the liquid away from the membrane 220 and hydrophobiclayer 224. The hydrophilic surface 232 can include any surface includinga biocompatible material, including for instance materials commonly usedin semiconductor devices, such as silicon (Si), SiO₂, SiN_(x), or otheroxides.

FIG. 4A depicts a hydrophobic delivery system 400 according to anotherembodiment of the invention. The system 400 includes a substrate 404 inwhich one or more cavities can be formed. The system 400 includes ahinged releasable membrane 402 connected to a hinged structure 412. Thehinged structure can include a low melting point material, such as ametal coated polymer layer including In. The membrane, and optionallythe handle or hinge 412, can be lined with a hydrophobic layer 224 onthe interior of the reservoir. In some embodiments of the invention, aplurality of layers can be deposited or formed upon the substrate 40,such as oxide layers 408 and nitride layers 406. In some embodiments ofthe invention, the system 400 includes control circuitry. In someembodiments of the invention, the system 400 includes and a metal layer410 in contact with the hinged structure 412. The system can alsoinclude electrode elements 420.

As is shown in FIG. 4A, a liquid 230 can be deposited in the reservoirand sealed with the membrane 402. Hydrophobic layer 224 can repel liquidin the reservoir 230 such that the liquid does not contact the membrane.The hydrophobic layer 224 can induce formation of an insulating airpocket between the surface of the liquid and the membrane 402.

FIG. 4B depicts the exemplary hydrophobic delivery system 400 of FIG. 4Aafter activation according to some embodiments of the invention. Afteractivation, membrane 402 and at least a portion of hydrophobic layer 224are partially released from the structure, for instance bymicro-electro-mechanical systems (MEMS) technology, exposing thereservoir to the local environment and allowing the release ofsubstances inside the reservoir. For example, in some embodiments of theinvention a hinge can be opened upon melting of a portion of a seal dueto local heating by a connected electrode. In such embodiments of theinvention, the membrane 402 can be opened to allow the rapid andcomplete release of substances within the reservoir without completelydisconnecting the membrane from the delivery device. In some embodimentsof the invention, the membrane 402 before activation is under mechanicalstress and, for instance, can be relieved from such stress uponactivation to facilitate opening of the membrane by curvature away fromthe reservoir cavity.

In the system of FIGS. 4A and 4B, for example, a melting temperature ofabout 157° C. can be required to open the reservoir for a membrane withdimensions of about 100 microns by 100 microns and having a thickness ofabout 1 micron including a seal composed of indium, corresponding to anenergy of about 20 micro Joules (μJ).

Structures according to FIGS. 4A and 4B can be fabricated by standardsemiconductor fabrication techniques, including, for instance, damasceneprocesses and standard lithography techniques used to fabricatemultilayer CMOS structures.

FIG. 5 is a block diagram of control circuitry that can be configured tocontrol the release of reservoir contents of a microchip substancedelivery device, according to an embodiment of the invention. FIG. 5depicts a control system 500 coupled to a power supply 514. The controlsystem 500 can include a microprocessor 508, memory 504, such as aprogrammable ROM, one or more sensors 506, a wirelesstransmitter/receiver 502, a demultiplexer circuit 1510 and a dispensingarray 512. Various components of the control system 500 includeintegrated circuits integrally formed as part of a delivery deviceincluding a hydrophobic layer. In FIG. 5 , for example, the dispensingarray 512 can include releasable membrane structures and reservoirs asdiscussed above. The control system 500 can be designed using standardcircuit design methods and built with standard silicon integratedcircuit technology.

The microprocessor 508 can generate control signals to the demultiplexercircuitry 510 to selectively activate one or more membranes of thedispensing array 512. In some embodiments of the invention,microprocessor 508 can generate control signals to activate substancerelease according to a programmed scheduled stored in the programmableROM. In another embodiment of the invention, the microprocessor 508 cangenerate control signals to activate substance release according tocontrol signals output from one or more sensors 506 that automaticallydetect when a substance is to be released according to local conditions.For instance, a delivery structure for pharmaceuticals can determinewhen doses of a given drug or medication are to be administered based atleast in part on analysis of biosensor input, such as local pH or localionic composition, and can activate of one or more membranes to releasean active pharmaceutical ingredient from one or more reservoirs based atleast in part on the sensed conditions. In yet another embodiment of theinvention, the microprocessor 508 can generate control signals toactivate substance release according to control signals output from awireless receiver based at least in part on remote commands provided bya health care provider or individual having an implantable or wearablesubstance delivery device.

In some embodiments of the invention, the power supply 514 can beimplemented as an internal power source, such as a bio-compatiblethin-film battery, that is integrated with the microchip substancedelivery device. For such embodiments of the invention, battery size,material, and packaging requirements limit the energy capacity, and itis for this reason that the energy requirements for substrate releaseare preferably minimized. In other embodiments of the invention, thepower supply 514 can be implemented as a wireless power delivery systemin which the power is transmitted to the control system 514 from anexternal source, such as by near field communication (NFC).

FIG. 6 depicts a flow diagram of an exemplary method 600 of fluiddelivery according to one or more embodiments of the present invention.The method 600 includes, for example, forming a hydrophobic liner on arelease membrane in a delivery structure reservoir, as shown at block602. The method 600 also includes providing a liquid in the reservoir,as shown at block 604. The method 600 also includes sealing thereservoir with a hydrophilic layer, as shown at block 606. The method600 also includes providing an electric current to the release membraneto dispense the liquid, as shown at block 608.

FIG. 7 depicts a flow diagram of an exemplary method 700 of fluiddelivery according to one or more embodiments of the present invention.The method 700 includes, for example, receiving a signal from a sensorconcerning an environmental condition, as shown at block 702.Alternatively, in some embodiments of the invention (not illustrated inFIG. 7 ), the method can include receiving a signal from an externaldevice or receiving a signal from a stored scheduling regimen. Themethod 700 also includes sending an electric current to a releasemembrane lined with a hydrophobic liner covering a delivery structurereservoir, as shown at block 704. The method 700 also includes rupturingthe membrane with the electric current, as shown at block 706.

As used herein, “liquid” is understood to mean a fluid aqueous material.Liquids in embodiments of the invention can include any liquid suitablefor delivery from a miniaturized delivery device. Liquids can includefor example, but not by limitation, pharmaceutical solutions andpreparations, nutritional solutions and preparations, nutraceuticalsolutions and preparations, catalysts, solvents, reagents, excipients,diluents, preservatives, and the like. In some embodiments of theinvention, a reservoir includes one or more active pharmaceuticalagents. In some embodiments of the invention, the reservoir includes anelectrolyte, such as a microbattery electrolyte. In some embodiments ofthe invention, digital delivery devices are interfaced to sensor systemsto provide an automatic closed-loop delivery systems

In some embodiments of the invention, liquid delivery devices areincluded in implantable or wearable drug delivery systems. For example,liquid delivery devices can be included in systems directed to providingtreatment and/or management of diabetes, pain, addiction, contraception,neurological disorders, or psychological disorders.

Embodiments of the invention can provide improved liquid deliverydevices by providing decreased power consumption for the delivery ofliquids in a miniaturized device. A hydrophobic layer adjacent themembrane can repel fluids from the membrane in the reservoir and therebyrelease materials from the structure with a lower energy expenditure.

Some embodiments of the invention provide improved liquid deliverydevices by reducing the risk of destruction or degradation and/orincreasing the integrity of liquids in the reservoir. A hydrophobiclayer adjacent the membrane can repel fluids from the membrane in thereservoir and reduces the risk of damage to the fluids that wouldotherwise occur upon activation through passing an electric currentthrough the membrane.

Various embodiments of the present invention are described herein withreference to the related drawings. Alternative embodiments can bedevised without departing from the scope of this invention. Althoughvarious connections and positional relationships (e.g., over, below,adjacent, etc.) are set forth between elements in the followingdescription and in the drawings, persons skilled in the art willrecognize that many of the positional relationships described herein areorientation-independent when the described functionality is maintainedeven though the orientation is changed. These connections and/orpositional relationships, unless specified otherwise, can be direct orindirect, and the present invention is not intended to be limiting inthis respect. Accordingly, a coupling of entities can refer to either adirect or an indirect coupling, and a positional relationship betweenentities can be a direct or indirect positional relationship. As anexample of an indirect positional relationship, references in thepresent description to forming layer “A” over layer “B” includesituations in which one or more intermediate layers (e.g., layer “C”) isbetween layer “A” and layer “B” as long as the relevant characteristicsand functionalities of layer “A” and layer “B” are not substantiallychanged by the intermediate layer(s).

The following definitions and abbreviations are to be used for theinterpretation of the claims and the specification. As used herein, theterms “comprises,” “comprising,” “includes,” “including,” “has,”“having,” “contains” or “containing,” or any other variation thereof,are intended to cover a non-exclusive inclusion. For example, acomposition, a mixture, process, method, article, or apparatus thatcomprises a list of elements is not necessarily limited to only thoseelements but can include other elements not expressly listed or inherentto such composition, mixture, process, method, article, or apparatus.

Additionally, the term “exemplary” is used herein to mean “serving as anexample, instance or illustration.” Any embodiment or design describedherein as “exemplary” is not necessarily to be construed as preferred oradvantageous over other embodiments or designs. The terms “at least one”and “one or more” are understood to include any integer number greaterthan or equal to one, i.e. one, two, three, four, etc. The terms “aplurality” are understood to include any integer number greater than orequal to two, i.e. two, three, four, five, etc. The term “connection”can include an indirect “connection” and a direct “connection.”

References in the specification to “one embodiment,” “an embodiment,”“an example embodiment,” etc., indicate that the embodiment describedcan include a particular feature, structure, or characteristic, butevery embodiment may or may not include the particular feature,structure, or characteristic. Moreover, such phrases are not necessarilyreferring to the same embodiment. Further, when a particular feature,structure, or characteristic is described in connection with anembodiment, it is submitted that it is within the knowledge of oneskilled in the art to affect such feature, structure, or characteristicin connection with other embodiments whether or not explicitlydescribed.

For purposes of the description hereinafter, the terms “upper,” “lower,”“right,” “left,” “vertical,” “horizontal,” “top,” “bottom,” andderivatives thereof shall relate to the described structures andmethods, as oriented in the drawing figures. The terms “overlying,”“atop,” “on top,” “positioned on” or “positioned atop” mean that a firstelement, such as a first structure, is present on a second element, suchas a second structure, wherein intervening elements such as an interfacestructure can be present between the first element and the secondelement. The term “direct contact” means that a first element, such as afirst structure, and a second element, such as a second structure, areconnected without any intermediary conducting, insulating orsemiconductor layers at the interface of the two elements.

The phrase “selective to,” such as, for example, “a first elementselective to a second element,” means that the first element can beetched and the second element can act as an etch stop.

The terms “about,” “substantially,” “approximately,” and variationsthereof, are intended to include the degree of error associated withmeasurement of the particular quantity based upon the equipmentavailable at the time of filing the application. For example, “about”can include a range of ±8% or 5%, or 2% of a given value.

As previously noted herein, for the sake of brevity, conventionaltechniques related to semiconductor device and integrated circuit (IC)fabrication may or may not be described in detail herein. By way ofbackground, however, a more general description of the semiconductordevice fabrication processes that can be utilized in implementing one ormore embodiments of the present invention will now be provided. Althoughspecific fabrication operations used in implementing one or moreembodiments of the present invention can be individually known, thedescribed combination of operations and/or resulting structures of thepresent invention are unique. Thus, the unique combination of theoperations described in connection with the fabrication of asemiconductor device according to the present invention utilize avariety of individually known physical and chemical processes performedon a semiconductor (e.g., silicon) substrate, some of which aredescribed in the immediately following paragraphs.

In general, the various processes used to form a micro-chip that will bepackaged into an IC fall into four general categories, namely, filmdeposition, removal/etching, semiconductor doping andpatterning/lithography. Deposition is any process that grows, coats, orotherwise transfers a material onto the wafer. Available technologiesinclude physical vapor deposition (PVD), chemical vapor deposition(CVD), electrochemical deposition (ECD), molecular beam epitaxy (MBE)and more recently, atomic layer deposition (ALD) among others.Removal/etching is any process that removes material from the wafer.Examples include etch processes (either wet or dry), andchemical-mechanical planarization (CMP), and the like. Semiconductordoping is the modification of electrical properties by doping, forexample, transistor sources and drains, generally by diffusion and/or byion implantation. These doping processes are followed by furnaceannealing or by rapid thermal annealing (RTA). Annealing serves toactivate the implanted dopants. Films of both conductors (e.g.,poly-silicon, aluminum, copper, etc.) and insulators (e.g., variousforms of silicon dioxide, silicon nitride, etc.) are used to connect andisolate transistors and their components. Selective doping of variousregions of the semiconductor substrate allows the conductivity of thesubstrate to be changed with the application of voltage. By creatingstructures of these various components, millions of transistors can bebuilt and wired together to form the complex circuitry of a modernmicroelectronic device. Semiconductor lithography is the formation ofthree-dimensional relief images or patterns on the semiconductorsubstrate for subsequent transfer of the pattern to the substrate. Insemiconductor lithography, the patterns are formed by a light sensitivepolymer called a photo-resist. To build the complex structures that makeup a transistor and the many wires that connect the millions oftransistors of a circuit, lithography and etch pattern transfer stepsare repeated multiple times. Each pattern being printed on the wafer isaligned to the previously formed patterns and slowly the conductors,insulators and selectively doped regions are built up to form the finaldevice.

The computer readable storage medium can be a tangible device that canretain and store instructions for use by an instruction executiondevice. The computer readable storage medium may be, for example, but isnot limited to, an electronic storage device, a magnetic storage device,an optical storage device, an electromagnetic storage device, asemiconductor storage device, or any suitable combination of theforegoing. A non-exhaustive list of more specific examples of thecomputer readable storage medium includes the following: a portablecomputer diskette, a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory (EPROMor Flash memory), a static random access memory (SRAM), a portablecompact disc read-only memory (CD-ROM), a digital versatile disk (DVD),a memory stick, a floppy disk, a mechanically encoded device such aspunch-cards or raised structures in a groove having instructionsrecorded thereon, and any suitable combination of the foregoing. Acomputer readable storage medium, as used herein, is not to be construedas being transitory signals per se, such as radio waves or other freelypropagating electromagnetic waves, electromagnetic waves propagatingthrough a waveguide or other transmission media (e.g., light pulsespassing through a fiber-optic cable), or electrical signals transmittedthrough a wire.

Computer readable program instructions described herein can bedownloaded to respective computing/processing devices from a computerreadable storage medium or to an external computer or external storagedevice via a network, for example, the Internet, a local area network, awide area network and/or a wireless network. The network may comprisecopper transmission cables, optical transmission fibers, wirelesstransmission, routers, firewalls, switches, gateway computers and/oredge servers. A network adapter card or network interface in eachcomputing/processing device receives computer readable programinstructions from the network and forwards the computer readable programinstructions for storage in a computer readable storage medium withinthe respective computing/processing device.

Computer readable program instructions for carrying out operations ofthe present invention may be assembler instructions,instruction-set-architecture (ISA) instructions, machine instructions,machine dependent instructions, microcode, firmware instructions,state-setting data, configuration data for integrated circuitry, oreither source code or object code written in any combination of one ormore programming languages, including an object oriented programminglanguage such as Smalltalk, C++, or the like, and procedural programminglanguages, such as the “C” programming language or similar programminglanguages. The computer readable program instructions may executeentirely on the user's computer, partly on the user's computer, as astand-alone software package, partly on the user's computer and partlyon a remote computer or entirely on the remote computer or server. Inthe latter scenario, the remote computer may be connected to the user'scomputer through any type of network, including a local area network(LAN) or a wide area network (WAN), or the connection may be made to anexternal computer (for example, through the Internet using an InternetService Provider). In some embodiments of the invention, electroniccircuitry including, for example, programmable logic circuitry,field-programmable gate arrays (FPGA), or programmable logic arrays(PLA) may execute the computer readable program instruction by utilizingstate information of the computer readable program instructions topersonalize the electronic circuitry, in order to perform aspects of thepresent invention.

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems), and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer readable program instructions.

These computer readable program instructions may be provided to aprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus to produce a machine, suchthat the instructions, which execute via the processor of the computeror other programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks. These computer readable program instructionsmay also be stored in a computer readable storage medium that can directa computer, a programmable data processing apparatus, and/or otherdevices to function in a particular manner, such that the computerreadable storage medium having instructions stored therein comprises anarticle of manufacture including instructions which implement aspects ofthe function/act specified in the flowchart and/or block diagram blockor blocks.

The computer readable program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other deviceto cause a series of operational steps to be performed on the computer,other programmable apparatus or other device to produce a computerimplemented process, such that the instructions which execute on thecomputer, other programmable apparatus, or other device implement thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods, and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof instructions, which comprises one or more executable instructions forimplementing the specified logical function(s). In some alternativeimplementations, the functions noted in the blocks may occur out of theorder noted in the Figures. For example, two blocks shown in successionmay, in fact, be executed substantially concurrently, or the blocks maysometimes be executed in the reverse order, depending upon thefunctionality involved. It will also be noted that each block of theblock diagrams and/or flowchart illustration, and combinations of blocksin the block diagrams and/or flowchart illustration, can be implementedby special purpose hardware-based systems that perform the specifiedfunctions or acts or carry out combinations of special purpose hardwareand computer instructions.

The descriptions of the various embodiments of the present inventionhave been presented for purposes of illustration, but are not intendedto be exhaustive or limited to the embodiments described. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the describedembodiments. The terminology used herein was chosen to best explain theprinciples of the embodiments of the invention, the practicalapplication or technical improvement over technologies found in themarketplace, or to enable others of ordinary skill in the art tounderstand the embodiments described herein.

What is claimed is:
 1. A liquid delivery apparatus comprising: asubstrate comprising a cavity formed in a surface of the substrate; amembrane connected to a hinged structure; a hydrophobic layer disposedon the membrane, the hydrophobic layer between the membrane and thecavity; and a drop of solution disposed in the cavity; wherein thehinged structure is configured to partially release the membrane and thehydrophobic layer to expose the cavity and release the drop of solution;and wherein the hydrophobic layer induces formation of an air pocketbetween the drop of solution and the membrane.
 2. The apparatus of claim1, wherein at least a portion of the membrane comprises a metal film. 3.The apparatus of claim 1 further comprising a hydrophilic layer disposedon a surface of the cavity opposite the membrane.
 4. The apparatus ofclaim 1, wherein the hydrophobic layer comprises a material selectedfrom the group consisting of fluorocarbon films, micro-structuredpolymers, carbon nanotubes, electrodeposited metal films, oxides, oxidecomposites, and patterned films.
 5. The apparatus of claim 1, whereinthe hydrophobic layer has a thickness of about 1 Angstrom (Å) to about500 nanometers (nm).
 6. The apparatus of claim 1 further comprising aliquid comprising the drop of solution in the cavity.
 7. The apparatusof claim 6, wherein the liquid comprises an active pharmaceutical agent.8. The apparatus of claim 6, wherein the liquid comprises a microbatteryelectrolyte.
 9. The apparatus of claim 6, wherein the hydrophobic layerlines a portion of the cavity.
 10. An electronic delivery devicecomprising: a dispensing array comprising a plurality of reservoirs,wherein each reservoir of the dispensing array comprises: a cavity; amembrane covering an opening of the cavity, the membrane connected to ahinged structure; a hydrophobic layer disposed on the membrane, thehydrophobic layer between the membrane and the cavity; and a drop ofsolution disposed in the cavity; a microprocessor in communication withthe dispensing array; and a wireless receiver in communication with themicroprocessor; wherein the hinged structure is configured to partiallyrelease the membrane and the hydrophobic layer to expose the cavity andrelease the drop of solution; and wherein the hydrophobic layer inducesformation of an air pocket between the drop of solution and themembrane.